Determination of moisture in hard gelatin capsules using near-infrared spectroscopy: applications to at-line process control of pharmaceutics.

A method is proposed in which diffuse reflectance near-infrared spectroscopy (NIR) is applied in an at-line process analytical interface to determine moisture content in bulk hard gelatin capsules. Capsule samples were equilibrated at various relative humidities and the moisture contents were determined using loss on drying (LOD). Different multivariate calibration methods using multiple linear regression (MLR) and partial least squares regression (PLSR) and various spectral pretreatments were compared. No sample pretreatment was required and the analysis time was 1-2 min. The investigated range for the moisture determination was 5.6-18.0% w/w and the root mean square error of prediction (RMSEP) value was 0.1% w/w.